Acne vulgaris and rosacea present therapeutic challenges due to their chronicity, potential for disfigurement, and psychosocial impact. Although pathophysiologically distinct, both conditions have major inflammatory components. Consequently, topical and systemic antimicrobial agents are routinely prescribed for extended periods. Emergence of resistant strains of Propionibacterium acnes, adverse events, and compliance issues associated with chronic systemic tetracycline use have led to new treatment approaches. At subantimicrobial doses, tetracyclines reduce inflammation via anticollagenolytic, antimatrix-degrading metalloproteinase, and cytokine down-regulating properties. Subantimicrobial dose (SD) doxycycline (Periostat 20 mg) has clinical utility in periodontitis and has been investigated in a double-blind, placebo-controlled trial in the treatment of moderate facial acne as well as in an open label study in the treatment of rosacea. The results of subantimicrobial dose doxycycline treatment in early trials support its benefits and further investigation in acne and rosacea.